The inferior performance of [ 68 Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [ 177 Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors.

Purpose: We aimed to investigate the potential of [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [ ¹⁷⁷ Lu]Lu-DOTATATE therapy.
Methods: Patients who received at least two cycles of [ ¹⁷⁷ Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [ ⁶⁸ Ga]Ga-DOTATATE and [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT within 3 weeks. The number of PET-positive lesions related to NETs and tumor sites was documented. Mann-Whitney U and chi-square tests were used to compare SUVmax levels of tracers and the number of detected metastases.
Results: Twelve patients (7 male, 5 female) who met the eligibility criteria were included in the study. Ten patients had grade 1-2 NET of various origins, and two had paraganglioma and pheochromocytoma. One hundred ninety-eight of 230 lesions (86%) were SSTR positive with a median SUVmax of 16.6 (2.2-76.5), and 88 of 230 lesions (38.2%) were [ ⁶⁸ Ga]Ga-FAPI-04 positive with a median SUVmax of 5.1 (2.3-21). Median SUVmax level and detected number of tumors were significantly higher in [ ⁶⁸ Ga]Ga-DOTATATE PET/CT (p=<0.001). [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT was completely (n:2) or almost completely (n:3) negative in 5 (42%) patients. Two (17%) patients had flip-flop SSTR/FAPI uptake in tumors. In four patients (33%), tumor uptake or the number of PET-positive lesions was inferior in [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT. Low-dose [ ¹⁷⁷ Lu]Lu-FAPI-46 dosimetry was performed on the FAPI-dominant patient; absorbed radiation doses per GBq were 1.26 Gy, 0.36 Gy, 0.32 Gy, and 0.2 Gy for kidneys, liver, spleen, and total body, respectively. The mean absorbed dose per GBq was 0.33 Gy for liver mass and 0.41 Gy for metastatic lymph nodes.
Conclusion: Our preliminary results demonstrated that [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [ ¹⁷⁷ Lu]Lu-DOTATATE therapy and had a limited role as an alternative diagnostic or theranostic agent. Further investigations with a larger patient population are required to determine the impact of [ ⁶⁸ Ga]Ga-FAPI-04 PET/CT on NETs.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)